Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-7 (of 7 Records) |
Query Trace: Birx DL[original query] |
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Risk factors for HIV-1 infection in a longitudinal, prospective cohort of adults from the Mbeya Region, Tanzania
Geis S , Maboko L , Saathoff E , Hoffmann O , Geldmacher C , Mmbando D , Samky E , Michael NL , Birx DL , Robb ML , Hoelscher M . J Acquir Immune Defic Syndr 2011 56 (5) 453-9 BACKGROUND: To control the global HIV epidemic targeted interventions to reduce the incidence of HIV infections are urgently needed until an effective HIV vaccine is available. This study describes HIV-1 incidence and associated risk factors in a general population cohort of adults from Mbeya Region, Tanzania, who participated in a vaccine preparedness study. METHODS: We conducted a closed prospective cohort study with six-monthly follow-up from 2002-2006, enrolling adults from the general population. HIV-1 incidence and risk factors for HIV-1 acquisition were analysed using Cox regression. RESULTS: We observed 2,578 sero-negative participants for a mean period of 3.06 PY (7,471 PY in total). Overall HIV-1 incidence was 1.35 per 100 PY (95% confidence interval [CI]=1.10-1.64/100 PY). The highest overall HIV-1 incidence was found in females from Itende village (1.55 per 100 PY, 95%CI=0.99-2.30/100 PY), the highest age-specific incidence was observed in semi-urban males aged 30-34 years (2.75 per 100 PY, 95%CI=0.75-7.04). HIV-1 acquisition was independently associated with female gender (hazard ratio [HR]=1.64, 95%CI=1.05-2.57), younger age at enrolment (age 18-19 vs. 35-39: HR=0.29, 95%CI=0.11-0.75), alcohol consumption (almost daily vs. none: HR 2.01, 95%CI=1.00-4.07), education level (secondary school vs. none: HR 0.39, 95%CI=0.17-0.89) and number of lifetime sex partners (more than five vs. one: HR 2.22, 95%CI=1.13-4.36). CONCLUSIONS: A high incidence of HIV was observed in this cohort, and incident infection was strongly associated with young age, alcohol consumption, low school education level and number of sex partners. Targeted interventions are needed to address the elevated risk associated with these factors. |
Multivalent dendrimeric compounds containing carbohydrates expressed on immune cells inhibit infection by primary isolates of HIV-1
Rosa Borges A , Wieczorek L , Johnson B , Benesi AJ , Brown BK , Kensinger RD , Krebs FC , Wigdahl B , Blumenthal R , Puri A , McCutchan FE , Birx DL , Polonis VR , Schengrund CL . Virology 2010 408 (1) 80-8 Specific glycosphingolipids (GSL), found on the surface of target immune cells, are recognized as alternate cell surface receptors by the human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein. In this study, the globotriose and 3'-sialyllactose carbohydrate head groups found on two GSL were covalently attached to a dendrimer core to produce two types of unique multivalent carbohydrates (MVC). These MVC inhibited HIV-1 infection of T cell lines and primary peripheral blood mononuclear cells (PBMC) by T cell line-adapted viruses or primary isolates, with IC(50)s ranging from 0.1 to 7.4 mug/ml. Inhibition of Env-mediated membrane fusion by MVC was also observed using a dye-transfer assay. These carbohydrate compounds warrant further investigation as a potential new class of HIV-1 entry inhibitors. The data presented also shed light on the role of carbohydrate moieties in HIV-1 virus-host cell interactions. |
The World Health Organization African region laboratory accreditation process: improving the quality of laboratory systems in the African region
Gershy-Damet GM , Rotz P , Cross D , Belabbes el H , Cham F , Ndihokubwayo JB , Fine G , Zeh C , Njukeng PA , Mboup S , Sesse DE , Messele T , Birx DL , Nkengasong JN . Am J Clin Pathol 2010 134 (3) 393-400 Few developing countries have established laboratory quality standards that are affordable and easy to implement and monitor. To address this challenge, the World Health Organization Regional Office for Africa (WHO AFRO) established a stepwise approach, using a 0- to 5-star scale, to the recognition of evolving fulfillment of the ISO 15189 standard rather than pass-fail grading. Laboratories that fail to achieve an assessment score of at least 55% will not be awarded a star ranking. Laboratories that achieve 95% or more will receive a 5-star rating. This stepwise approach acknowledges to laboratories where they stand, supports them with a series of evaluations to use to demonstrate improvement, and recognizes and rewards their progress. WHO AFRO's accreditation process is not intended to replace established ISO 15189 accreditation schemes, but rather to provide an interim pathway to the realization of international laboratory standards. Laboratories that demonstrate outstanding performance in the WHO-AFRO process will be strongly encouraged to enroll in an established ISO 15189 accreditation scheme. We believe that the WHO-AFRO approach for laboratory accreditation is affordable, sustainable, effective, and scalable. |
A phase 1/2 study of a multiclade HIV-1 DNA plasmid prime and recombinant adenovirus serotype 5 boost vaccine in HIV-uninfected East Africans (RV 172)
Kibuuka H , Kimutai R , Maboko L , Sawe F , Schunk MS , Kroidl A , Shaffer D , Eller LA , Kibaya R , Eller MA , Schindler KB , Schuetz A , Millard M , Kroll J , Dally L , Hoelscher M , Bailer R , Cox JH , Marovich M , Birx DL , Graham BS , Michael NL , de Souza MS , Robb ML . J Infect Dis 2010 201 (4) 600-7 BACKGROUND: Human immunodeficiency virus (HIV) vaccine development remains a global priority. We describe the safety and immunogenicity of a multiclade DNA vaccine prime with a replication-defective recombinant adenovirus serotype 5 (rAd5) boost. METHODS: The vaccine is a 6-plasmid mixture encoding HIV envelope (env) subtypes A, B, and C and subtype B gag, pol, and nef, and an rAd5 expressing identical genes, with the exception of nef. Three hundred and twenty-four participants were randomized to receive placebo (n=138), a single dose of rAd5 at 10(10) (n = 24) or 10(11) particle units (n = 24), or DNA at 0, 1, and 2 months, followed by rAd5 at either 10(10) (n= 114) or 10(11) particle units (n = 24) boosting at 6 months. Participants were followed up for 24 weeks after the final vaccination. RESULTS: The vaccine was safe and well tolerated. HIV-specific T cell responses were detected in 63% of vaccinees. Titers of preexisting Ad5 neutralizing antibody did not affect the frequency and magnitude of T cell responses in prime-boost recipients but did affect the response rates in participants that received rAd5 alone (P = .037). CONCLUSION: The DNA/rAd5 vaccination regimen was safe and induced HIV type 1 multi-clade T cell responses, which were not significantly affected by titers of preexisting rAd5 neutralizing antibody. Trial Registration. ClinicalTrials.gov identifier: NCT00123968 . |
Short communication: HIV type 1 genetic diversity among tea plantation workers in Kericho, Kenya
Arroyo MA , Sateren WB , Foglia G , Kibaya R , Langat L , Wasunna M , Bautista CT , Scott PT , Shaffer DN , Robb ML , Michael NL , Birx DL , McCutchan FE . AIDS Res Hum Retroviruses 2009 25 (11) 1061-4 In preparation for HIV-1 vaccine trials in Kenya, 2801 study volunteers, from a tea plantation in Kericho, were recruited as part of a prospective vaccine cohort development study. Cryopreserved plasma was available from 401 HIV-positive volunteers, and was the source of viral RNA for genotyping by the multiregion hybridization assay (MHA). Logistic regression was performed to determine association of risk factors and HIV-1 recombinant and dual infections. At baseline, HIV-1 subtype A was the dominant circulating pure subtype (56%), followed by subtype D (10%) and C (5%). Recombinant HIV-1 strains accounted for almost one-third of all infections (29%), with 7% infected with a dual strain of the HIV-1 variants described. A higher number of HIV-1 recombinant and dual infections was observed among volunteers who were 18-24 and 25-29 years of age, affiliated with the Luo tribe, had been married two or more times, reported not being circumcised, and had STI symptoms in the past 6 months. Adjusted odds ratios (AOR) significantly associated with HIV-1 recombinant and dual infection were age difference from current spouse (5-9 years; AOR = 2.5, 95% CI = 1.2-5.3 and > or = 10 years; AOR = 3.1, 95% CI = 1.5-6.4) and reported STI symptoms in the past 6 months (AOR = 4.8, 95% CI = 2.0-11.6), respectively. In conclusion, our results suggest that there is considerable heterogeneity with respect to HIV-1 subtype diversity in this population that should be considered in the planning for future vaccine trials in the region. |
HIV-1 incidence rates and risk factors in agricultural workers and dependents in rural Kenya: 36-month follow-up of the Kericho HIV cohort study
Shaffer DN , Ngetich IK , Bautista CT , Sawe FK , Renzullo PO , Scott PT , Kibaya RM , Imbuki KO , Michael NL , Birx DL , Wasunna MK , Robb ML . J Acquir Immune Defic Syndr 2009 53 (4) 514-21 BACKGROUND: Incidence data from prospective cohort studies using rigorous laboratory methods are important in designing and evaluating HIV vaccine and therapeutic clinical trials and health care programs. We report 36-month HIV-1 incidence rates and demographic and psychosocial risks from the Kericho cohort in rural Kenya's southern Rift Valley Province. METHODS: Thirty-six month, prospective, closed, observational cohort study of adult plantation workers and dependents followed biannually. HIV-1 incidence rates per 100 person-years (py) were calculated, and Cox regression analyses were used to estimate hazards ratios (HR) associated with seroconversion. RESULTS: Two thousand four hundred volunteers (mean age +/- SD = 30.1 +/- 8.5 years; 36.5% women) participated. Twenty-nine new HIV cases were identified in year 1 of follow-up, which increased to cumulative totals of 49 and 63 cases in years 2 and 3, respectively. The corresponding 1-, 2-, and 3-year incidence rates were 1.41 [95% confidence interval (CI) = 0.95-2.02], 1.16 (95% CI = 0.86-1.54), and 1.00 (95% CI = 0.77-1.28) per 100 py. Risk factors associated with HIV seroconversion included the following: of the Luo tribe (HR = 3.31; 95% CI = 1.65-6.63), marriage more than once (HR = 2.83; 95% CI = 1.20-6.69), self-reported male circumcision (HR = 0.32; 95% CI = 0.17-0.60), history of sexually transmitted infection (HR = 2.40; 95% CI = 1.09-5.26), history of substance abuse during sex (HR = 2.44; 95% CI = 1.16-5.13), and history of transactional sex (HR = 3.30; 95% CI = 1.79-6.09). CONCLUSIONS: HIV-1 incidence rates were relatively low in adult plantation workers and dependents in rural Kenya. Cohorts including higher risk populations (eg, commercial sex workers) warrant consideration for regional HIV preventive vaccine trials. Even low incidence, well-described cohorts generate valuable epidemiological clinical trial data. |
Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand
Rerks-Ngarm S , Pitisuttithum P , Nitayaphan S , Kaewkungwal J , Chiu J , Paris R , Premsri N , Namwat C , de Souza M , Adams E , Benenson M , Gurunathan S , Tartaglia J , McNeil JG , Francis DP , Stablein D , Birx DL , Chunsuttiwat S , Khamboonruang C , Thongcharoen P , Robb ML , Michael NL , Kunasol P , Kim JH , MOPH-TAVEG Investigators . N Engl J Med 2009 361 (23) 2209-20 BACKGROUND: The development of a safe and effective vaccine against the human immunodeficiency virus type 1 (HIV-1) is critical to pandemic control. METHODS: In a community-based, randomized, multicenter, double-blind, placebo-controlled efficacy trial, we evaluated four priming injections of a recombinant canarypox vector vaccine (ALVAC-HIV [vCP1521]) plus two booster injections of a recombinant glycoprotein 120 subunit vaccine (AIDSVAX B/E). The vaccine and placebo injections were administered to 16,402 healthy men and women between the ages of 18 and 30 years in Rayong and Chon Buri provinces in Thailand. The volunteers, primarily at heterosexual risk for HIV infection, were monitored for the coprimary end points: HIV-1 infection and early HIV-1 viremia, at the end of the 6-month vaccination series and every 6 months thereafter for 3 years. RESULTS: In the intention-to-treat analysis involving 16,402 subjects, there was a trend toward the prevention of HIV-1 infection among the vaccine recipients, with a vaccine efficacy of 26.4% (95% confidence interval [CI], -4.0 to 47.9; P=0.08). In the per-protocol analysis involving 12,452 subjects, the vaccine efficacy was 26.2% (95% CI, -13.3 to 51.9; P=0.16). In the modified intention-to-treat analysis involving 16,395 subjects (with the exclusion of 7 subjects who were found to have had HIV-1 infection at baseline), the vaccine efficacy was 31.2% (95% CI, 1.1 to 51.2; P=0.04). Vaccination did not affect the degree of viremia or the CD4+ T-cell count in subjects in whom HIV-1 infection was subsequently diagnosed. CONCLUSIONS: This ALVAC-HIV and AIDSVAX B/E vaccine regimen may reduce the risk of HIV infection in a community-based population with largely heterosexual risk. Vaccination did not affect the viral load or CD4+ count in subjects with HIV infection. Although the results show only a modest benefit, they offer insight for future research. (ClinicalTrials.gov number, NCT00223080.) Copyright 2009 Massachusetts Medical Society. |
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